N-叔丁基-α-苯基硝酮对大鼠脊髓损伤后神经生长因子表达的影响

Effect of α-phenyl-N-tert-butylinitrone on Expression of Nerve Growth Factor in Spinal Cord Injured Rats

目的：观察N-叔丁基-α-苯基硝酮（PBN）对脊髓损伤大鼠脊髓组织和血清中神经生长因子（NGF）蛋白表达的影响。方法174只健康雌性Sprague-Dawley大鼠，体质量180～220 g，随机分为正常对照组（n=54）、生理盐水（NS）对照组（n=60）和PBN组（n=60），每时间段6只。鞘内置管后，采用自行改制的O型NYU装置建立大鼠脊髓损伤模型。PBN组鞘内注射PBN 3 mg （15μl）， NS对照组注射NS 15μl，术后30 min第1次注射，连续注射7 d，每天1次。术前3 d和1 d，以及术后1 d、5 d、10 d、15 d、20 d、25 d、30 d和35 d对NS对照组和PBN组进行Basso-Beattie-Bresnahan （BBB）运动功能评价，并在术后1 h、12 h、24 h、48 h、3 d、7 d、14 d和21 d各组取血清和脊髓组织测定NGF水平。结果术后血清中NGF蛋白含量出现明显改变，而脊髓组织中含量变化不明显。血清NGF/总蛋白比值48 h时达到峰值， NS对照组（0.92%±0.02%）与PBN组（0.77%±0.05%）相比有显著性差异（P=0.021）。两组大鼠BBB评分在伤后第10天开始升高，PBN组恢复程度明显好于NS对照组（P〈0.01）。结论 PBN能有效降低脊髓损伤大鼠血清中NGF蛋白的表达，促进神经功能恢复。

Objective To explore the effect ofα-phenyl-N-tert-butylinitrone （PBN） on expression of nerve growth factor （NGF） in se-rum and spinal cord tissue in rats after spinal cord injury （SCI）. Methods 174 female Sprague-Dawley rats were randomly assigned to fol-lowing groups：normal control group （n=54）, normal saline control group （NS group, n=60, intrathecally injected normal saline 15 μl）, and PBN group （n=60, intrathecally injected PBN, 3 mg, 15 μl）. The model was established with New York University blow device （150 kDyne, 1 s dwell time）. PBN was intrathecally injected into the damaged areas 30 min after operation, then once a day for 7 days. The Basso-Beattie-Bresnahan （BBB） Locomotor Rating Scale was used to assess the rats 3 days and 1 day before, and 1 day, 5 days, 10 days, 15 days, 20 days, 25 days, 30 days and 35 days after SCI. NGF in the injured spinal cord tissue and serum was measured 1 h, 12 h, 24 h, 48 h, 3 days, 7 days, 14 days and 21 days after SCI. Results NGF increased in serum but not in spinal cord. The ratio of NGF/total protein in serum rose and peaked 48 h after SCI, and the ratio was higher in NS group （0.92%±0.02%） than in PBN group （0.77%±0.05%） （P=0.021）. BBB scores in-creased from the 9th day, and PBN group improved better than NS group （P〈0.01）. Conclusion PBN could reduce the expression of NGF in the SCI rats, and promote the recovery of neurol function.